BRAIN TUMOR

OUTLINE
I. Definition
II. Types and Grades of Brain Tumor
III. Risk Factors
IV. Signs and Symptoms
V. Diagnosis
VI. Management

Definition
A brain tumor is an abnormal growth of cells inside the brain or skull in which cells grow
and multiply uncontrollably, seemingly unchecked by the mechanisms that control normal cells;
some are benign, others malignant.
Causes of brain tumors
Medical science neither knows what causes brain tumors nor how to prevent primary
tumors that start in the brain. People most at risk for brain tumors include those who have:

 cancer elsewhere in the body

 prolonged exposure to pesticides, industrial solvents, and other chemicals
 inherited diseases, such as neurofibromatosis

Brain tumors are thought to arise when certain genes on the chromosomes of a cell are
damaged and no longer function properly. These genes normally regulate the rate at which the
cell divides (if it divides at all) and repair genes that fix defects of other genes, as well as genes
that should cause the cell to self-destruct if the damage is beyond repair. In some cases, an
individual may be born with partial defects in one or more of these genes. Environmental
factors may then lead to further damage. In other cases, the environmental injury to the genes
may be the only cause. It is not known why some people in an "environment" develop brain
tumors, while others do not.
Once a cell is dividing rapidly and internal mechanisms to check its growth are damaged,
the cell can eventually grow into a tumor. Another line of defense may be the body's immune
system, which optimally would detect the abnormal cell and kill it. Tumors may produce
substances that block the immune system from recognizing the abnormal tumor cells and
eventually overpower all internal and external deterrents to its growth.
A rapidly growing tumor may need more oxygen and nutrients than can be provided by
the local blood supply intended for normal tissue. Tumors can produce substances
called angiogenesis factors that promote the growth of blood vessels. The new vessels that
grow increase the supply of nutrients to the tumor, and, eventually, the tumor becomes
dependent on these new vessels. Research is being done in this area, but more extensive
research is necessary to translate this knowledge into potential therapies.
 Types of Brain Tumors
More than 150 different brain tumors have been documented, but the two main groups
of brain tumors are termed primary and metastatic.

Primary brain tumors include tumors that originate from the tissues of the brain or the
brain's immediate surroundings. Primary tumors are categorized as glial (composed of glial
cells) or non-glial (developed on or in the structures of the brain, including nerves, blood
vessels and glands) and benign or malignant.

Metastatic brain tumors include tumors that arise elsewhere in the body (such as the
breast or lungs) and migrate to the brain, usually through the bloodstream. Metastatic tumors
are considered cancer and are malignant. Metastatic tumors to the brain affect nearly one in
four patients with cancer, or an estimated 150,000 people a year. Up to 40 percent of people
with lung cancer will develop metastatic brain tumors. In the past, the outcome for patients
diagnosed with these tumors was very poor, with typical survival rates of just several weeks.
More sophisticated diagnostic tools, in addition to innovative surgical and radiation
approaches, have helped survival rates expand up to years; and also allowed for an improved
quality of life for patients following diagnosis.

Types of Benign Brain Tumors

 Chordomas are benign, slow-growing tumors that are most prevalent in people ages 50
to 60. Their most common locations are the base of the skull and the lower portion of the
spine. Although these tumors are benign, they may invade the adjacent bone and put pressure
on nearby neural tissue. These are rare tumors, contributing to only 0.2 percent of all primary
brain tumors.
 Craniopharyngiomas typically are benign, but are difficult tumors to remove because of
their location near critical structures deep in the brain. They usually arise from a portion of
the pituitary gland (the structure that regulates many hormones in the body), so nearly all
patients will require some hormone replacement therapy.
 Gangliocytomas, gangliomas and anaplastic gangliogliomas are rare tumors that
include neoplastic nerve cells that are relatively well-differentiated, occurring primarily in
young adults.
 Glomus jugulare tumors most frequently are benign and typically are located just under
the skull base, at the top of the jugular vein. They are the most common form of glomus tumor.
However, glomus tumors, in general, contribute to only 0.6 percent of neoplasms of the head
and neck.
 Meningiomas are the most common benign intracranial tumors, comprising 10 to 15
percent of all brain neoplasms, although a very small percentage are malignant. These tumors
 originate from the meninges, the membrane-like structures that surround the brain and spinal
cord.
 Pineocytomas are generally benign lesions that arise from the pineal cells, occurring
predominantly in adults. They are most often well-defined, noninvasive, homogeneous and
slow-growing.
 Pituitary adenomas are the most common intracranial tumors after gliomas,
meningiomas and schwannomas. The large majority of pituitary adenomas are benign and fairly
slow-growing. Even malignant pituitary tumors rarely spread to other parts of the body.
Adenomas are by far the most common disease affecting the pituitary. They commonly affect
people in their 30s or 40s, although they are diagnosed in children, as well. Most of these
tumors can be treated successfully.
 Schwannomas are common benign brain tumors in adults. They arise along nerves,
comprised of cells that normally provide the "electrical insulation" for the nerve cells.
Schwannomas often displace the remainder of the normal nerve instead of invading it. Acoustic
neuromas are the most common schwannoma, arising from the eighth cranial nerve,
or vestibularcochlear nerve, which travels from the brain to the ear. Although these tumors are
benign, they can cause serious complications and even death if they grow and exert pressure
on nerves and eventually on the brain. Other locations include the spine and, more rarely, along
nerves that go to the limbs.

Types of Malignant Brain Tumors

Gliomas are the most prevalent type of adult brain tumor, accounting for 78 percent of
malignant brain tumors. They arise from the supporting cells of the brain, called the glia. These
cells are subdivided into astrocytes, ependymal cells and oligodendroglial cells (or oligos). Glial
tumors include the following:

 Astrocytomas are the most common glioma, accounting for about half of all primary
brain and spinal cord tumors. Astrocytomas develop from star-shaped glial cells called
astrocytes, part of the supportive tissue of the brain. They may occur in many parts of the brain,
but most commonly in the cerebrum. People of all ages can develop astrocytomas, but they are
more prevalent in adults — particularly middle-aged men. Astrocytomas in the base of the
brain are more prevalent in children or younger people and account for the majority of
children's brain tumors. In children, most of these tumors are considered low-grade, while in
adults, most are high-grade.
 Ependymomas are derived from a neoplastic transformation of the ependymal cells
lining the ventricular system and account for two to three percent of all brain tumors. Most are
well-defined, but some are not.
 Glioblastoma multiforme (GBM) is the most invasive type of glial tumor. These tumors
tend to grow rapidly, spread to other tissue and have a poor prognosis. They may be composed
of several different kinds of cells, such as astrocytes and oligodendrocytes. GBM is more
common in people ages 50 to 70 and are more prevalent in men than women.
 Medulloblastomas usually arise in the cerebellum, most frequently in children. They are
high-grade tumors, but they are usually responsive to radiation and chemotherapy.
 Oligodendrogliomas are derived from the cells that make myelin, which is the insulation
for the wiring of the brain.

Other Types of Brain Tumors

 Hemangioblastomas are slow-growing tumors, commonly located in the cerebellum.

They originate from blood vessels, can be large in size and often are accompanied by a cyst.
These tumors are most common in people ages 40 to 60 and are more prevalent in men than
women.
 Rhabdoid tumors are rare, highly aggressive tumors that tend to spread throughout the
central nervous system. They often appear in multiple sites in the body, especially in the
kidneys. They are more prevalent in young children, but also can occur in adults.
 Whether a brain tumor is benign, malignant, or metastatic, all are potentially life-
threatening. Enclosed within the bony skull, the brain cannot expand to make room for a
growing mass. As a result, the tumor compresses and displaces normal brain tissue. Some brain
tumors cause a blockage of cerebrospinal fluid (CSF) that flows around and through the brain.
This blockage increases intracranial pressure and can enlarge the ventricles (hydrocephalus).
Some brain tumors cause swelling (edema). Size, pressure, and swelling all create "mass effect,"
which cause many of the symptoms (Fig. 1).

Figure 1. Brain tumors may grow from nerves (neuroma),

dura (meningioma), or pituitary gland (craniopharyngioma or
pituitary adenoma). They may also grow from the brain tissue
itself (glioma). As they grow they may compress normal tissue
and cause symptoms.

The World Health Organization (WHO) developed a classification and grading system to
standardize communication, treatment planning, and predict outcomes for brain tumors.
Tumors are classified by their cell type and grade by viewing the cells, usually taken during a
biopsy, under a microscope.
Cell type. Refers to the cell of origin of the tumor. For example, nerve cells (neurons) and
support cells (glial and schwann cells) give rise to tumors. About half of all primary brain tumors
grow from glial cells (gliomas). There are many types of gliomas because there are different
kinds of glial cells.
Grade. Refers to the way tumor cells look under the microscope and is an indication of
aggressiveness (e.g., low grade means least aggressive and high grade means most aggressive)
Tumors often have a mix of cell grades and can change as they grow. Differentiated and
anaplastic are terms used to describe how similar or abnormal the tumor cells appear
compared to normal cells.
The World Health Organization (WHO) has developed a grading system to indicate a tumor's
malignancy or benignity based on its histological features under a microscope.

 Most malignant
 Rapid growth, aggressive
 Widely infiltrative
 Rapid recurrence
 Necrosis prone

World Health Organization (WHO) Brain Tumor Grades

Grade Characteristics Tumor Types

Low WHO  Least malignant  Pilocytic astrocytoma
Grade Grade I (benign)  Craniopharyngioma
 Possibly curable via  Gangliocytoma
surgery alone  Ganglioglioma
 Non-infiltrative
 Long-term survival
 Slow growing
 Grade Characteristics Tumor Types
 Relatively slow
 "Diffuse" Astrocytoma
growing
 Pineocytoma
WHO  Somewhat infiltrative
 Pure
Grade II  May recur as higher
oligodendroglioma
grade

 Anaplastic
astrocytoma
 Malignant  Anaplastic
WHO
 Infiltrative ependymoma
Grade III
 Tend to recur as  Anaplastic
higher grade oligodendroglioma
High
Grade  Most malignant
 Gliobastoma
 Raid growth,
multiforme (GBM)
aggressive
WHO  Pineoblastoma
 Widely infiltrative
Grade IV  Medulloblastoma
 Rapid recurrence
 Ependymoblastoma
 Necrosis prone

Signs and symptoms

Tumors can affect the brain by destroying normal tissue, compressing normal tissue, or
increasing intracranial pressure. Symptoms vary depending on the tumor’s type, size, and
location in the brain. General symptoms include:

 headaches that tend to worsen in the morning

 seizures
 stumbling, dizziness, difficulty walking
 speech problems (e.g., difficulty finding the right word)
 vision problems, abnormal eye movements
 weakness on one side of the body
 increased intracranial pressure, which causes drowsiness, headaches, nausea and
vomiting, sluggish responses

Figure 2. Brain tumor symptoms are related to the functional areas of the brain in which they
are located.

Specific symptoms include:

  Frontal lobe tumors may cause: behavioral and emotional changes; impaired judgment,
motivation or inhibition; impaired sense of smell or vision loss; paralysis on one side of
the body; reduced mental abilities and memory loss.
 Parietal lobe tumors may cause: impaired speech; problems writing, drawing or naming;
lack of recognition; spatial disorders and eye-hand coordination.
 Occipital lobe tumors may cause: vision loss in one or both eyes, visual field cuts;
blurred vision, illusions, hallucinations
 Temporal lobe tumors may cause: difficulty speaking and understanding language;
short-term and long-term memory problems; increased aggressive behavior
 Brainstem tumors may cause: behavioral and emotional changes, difficulty speaking and
swallowing, drowsiness, hearing loss, muscle weakness on one side of the face (e.g.,
head tilt, crooked smile), muscle weakness on one side of the body, uncoordinated gait,
drooping eyelid or double vision, and vomiting.
 Pituitary gland tumors may cause: increased secretion of hormones (Cushing’s Disease,
acromegaly), a stop in menstruation, abnormal secretion of milk, and decreased libido.

Diagnosis
First, the doctor will obtain the personal and family medical history and perform a complete
physical examination. A neurological exam to check mental status and memory, cranial nerve
function (sight, hearing, smell, tongue and facial movement), muscle strength, coordination,
reflexes, and response to pain are performed. Additional tests may include:

 Audiometry, a hearing test performed by an audiologist, detects hearing loss due to

tumors near the cochlear nerve (e.g., acoustic neuroma).

 An endocrine evaluation measures hormone levels in your blood or urine to detect

abnormal levels caused by pituitary tumors (e.g., Cushing’s Disease).

 A visual field acuity test is performed by a neuro-ophthalmologist to detect vision loss

and missing areas in your field of view.
 A lumbar puncture (spinal tap) may be performed to examine cerebrospinal fluid for
tumor cells, proteins, infection, and blood.

Imaging tests

 Computed Tomography (CT) scan uses an X-ray beam and a computer to view

anatomical structures. It views the brain in slices, layer-by-layer, taking a picture of each
slice. A dye (contrast agent) may be injected into the bloodstream. CT is very useful for
viewing changes in bony structures.
 Magnetic Resonance Imaging (MRI) scan uses a magnetic field and radiofrequency
waves to give a detailed view of the soft tissues of the brain. It views the brain 3-
dimensionally in slices that can be taken from the side or from the top as a cross-
section. A dye (contrast agent) may be injected into the bloodstream. MRI is very useful
to evaluate brain lesions and their effects on surrounding brain (Fig. 3).
Figure 3. MRI scans of a benign and malignant brain tumor. Benign tumors have well defined
edges and are more easily removed surgically. Malignant tumors have an irregular border that
invades normal tissue with finger-like projections making surgical removal more difficult.

Biopsy
If a diagnosis cannot be made clearly from the scans, a biopsy may be performed to
determine what type of tumor is present. Biopsy is a procedure to remove a small amount of
tumor cells to be examined by a pathologist under a microscope. A biopsy can be taken as part
of an open surgical procedure to remove the tumor or as a separate diagnostic procedure,
known as a needle biopsy. A small burr hole is drilled in the skull so that a hollow needle can be
guided into the tumor and a tissue sample removed (Fig. 4). A stereotactic frame and a
computer are often used to help precisely locate the tumor and direct the needle to deep
tumors in critical locations.
Biomarkers or genetic mutations found in the tumor may help determine prognosis. These
include: IDH1, IDH2, MGMT, and 1p/19q co-deletion.

Figure 4. During a needle biopsy, a hollow cannula is inserted into the tumor. Small biting
instruments remove bits of tumor for the pathologist to examine and determine the exact
tumor cell type.
Who treats brain tumors?
The team may include a neurosurgeon, oncologist, radiation oncologist, radiologist,
neurologist, and neuro-ophthalmologist.
Management
Treatment options vary depending on the type, grade, size and location of the tumor;
whether it has spread; and the age and general health. The goal of treatment may be curative
or focus on relieving symptoms (palliative care). Treatments are often used in combination with
one another. The goal is to remove all or as much of the tumor as possible through surgery to
minimize the chance of recurrence. Radiation therapy and chemotherapy are used to treat
tumors that cannot be removed by surgery alone. For example, surgery may remove the bulk of
the tumor and a small amount of residual tumor near a critical structure can later be treated
with radiation.
Observation
Sometimes the best treatment is observation. For example, benign, slow growing
tumors that are small and have few symptoms may be observed with routine MRI scans every
year until their growth or symptoms necessitate surgery. Observation may be the best option
for people who are older or with other health conditions.
Medication
Medications are used to control some of the common side effects of brain tumors.
  Steroids, such as dexamethasone (Decadron), are used to reduce swelling and fluid
build-up (edema) around the tumor. Because steroids can cause stomach ulcers and
gastric reflux, famotidine (Pepcid) or pantoprazole (Protonix) are prescribed to reduce
the amount of acid produced in the stomach.
 Furosemide (Lasix) or mannitol (Osmitrol) may be used to control edema and swelling.
 Anticonvulsants are used to prevent or control seizures. The most common ones include
phenytoin (Dilantin), valproic acid (Depakote), carbamazepine (Tegretol), and
levetiracetam (Keppra).

Surgery
Surgery is the treatment of choice for brain tumors that can be reached without causing major
injury to vital parts of the brain. Surgery can help to refine the diagnosis, remove as much of
the tumor as possible, and release pressure within the skull. A neurosurgeon performs
a craniotomy to open the skull and remove the tumor (Fig 5). Sometimes only part of the tumor
is removed if it is near critical areas of the brain. A partial removal can still relieve symptoms.
Radiation or chemotherapy may be used on the remaining tumor cells.
Image-guided surgery technologies, tumor fluorescence, intraoperative MRI/CT, and functional
brain mapping have improved the surgeon’s ability to precisely locate the tumor, define the
tumor’s borders, avoid injury to vital brain areas, and confirm the amount of tumor removal
while in the operating room.

Figure 5. Surgery involves cutting a window in the skull

(craniotomy) to remove the tumor.

Laser Interstitial Thermal Therapy

Laser ablation is a minimally invasive treatment that transmits heat to “cook” brain
tumors from the inside out. A probe is inserted to the tumor through a burr hole in the skull.
The laser catheter is guided with real-time MRI.
Radiation
Radiation therapy uses controlled high-energy rays to treat brain tumors. Radiation
damages the DNA inside cells, making them unable to divide and grow. The benefits of
radiation are not immediate but occur with time. Aggressive tumors, whose cells divide rapidly,
tend to respond quickly to radiation. Over time, the abnormal cells die and the tumor may
shrink. Benign tumors, whose cells divide slowly, may take months to show an effect.
Pinpoint accuracy is critical so that the lethal dose is applied only to the tumor and not
to surrounding healthy tissues. There are two ways to deliver radiation, external and internal
beams.
External beam radiation is delivered from outside the body by a machine that aims high-
energy rays (x-rays, gamma rays) at the tumor (Fig. 6).
 Figure 6. A machine rotates around the patient, aiming radiation
beams at the tumor. The radiation beams are shaped to match the tumor and minimize
exposure to normal brain tissue.

 Stereotactic radiosurgery (SRS) delivers a high dose of radiation during a single session.

Frames and masks are used to keep the patient immobile.
 Fractionated radiotherapy delivers lower doses of radiation over many visits. Patients
return daily over several weeks to receive the complete radiation dose.
 Proton beam therapy delivers accelerated proton energy to the tumor at a specific
depth. The radiation beam does not go beyond the tumor.
 Whole brain radiotherapy (WBRT) delivers the radiation dose to the entire brain. It may
be used to treat multiple brain tumors and metastases.

Internal radiation (brachytherapy) is delivered from inside the body by radioactive seeds
surgically placed inside the tumor. After the patient undergoes a craniotomy to remove the
tumor, the radioactive implants are placed inside the empty tumor cavity. The radiation dose is
delivered to the first few millimeters of tissue in the cavity where malignant cells may still
remain. Patients have no risk of radiation injury to other parts of their own body or to others
around them because the dose is short lived.
Chemotherapy
Chemotherapy drugs work by disrupting cell division. Over time, chemotherapy causes
the abnormal cells to die and the tumor may shrink. This treatment can also damage normal
cells, but they can repair themselves better than abnormal cells. Treatment is delivered in
cycles with rest periods in between to allow the body to rebuild healthy cells.
Chemotherapy drugs can be taken orally as a pill, intravenously (IV), or as a wafer placed
surgically into the tumor. The drugs most commonly used to treat brain tumors are
temozolomide (Temodar) and bevacizumab (Avastin). The most common side effects are
nausea, low blood counts, infections, fatigue, constipation, and headaches. Chemotherapy is
also used to increase tumor cell death during radiation therapy.
Some chemotherapy drugs (BCNU wafer) are applied locally to the tumor bed after the
tumor has been removed. By applying it directly to the diseased area of the brain, side effects
are limited and the drug has a more beneficial effect.
Chemotherapy is typically used for high-grade gliomas; it is not routinely used for benign
tumors.

Figure 7. Chemotherapy for high-grade gliomas is usually taken

as a pill daily for a set period of time called a cycle. The drug circulates
through the bloodstream to the brain where it crosses the blood-
brain-barrier to the tumor.
 

Adjunct therapies

 Immunotherapy or biotherapy activates the immune system (T-cells and antibodies) to

destroy tumor cells. Research is exploring ways to prevent or treat cancer through
vaccines.
 Gene therapy uses viruses or other vectors to introduce new genetic material into
tumor cells. This experimental therapy can cause tumor cells to die or increase their
susceptibility to other cancer therapies.
 Hyperbaric oxygen uses oxygen at higher than normal levels to promote wound healing
and help fight infection. It may also improve the tumor’s responsiveness to radiation
and is being studied experimentally. Currently it is being used to help the body naturally
remove dead tumor cells and treat radiation necrosis.

Tumor Treating Fields or TTFields

TTFields slows and reverses tumor growth by keeping cells from dividing. TTFields is used for
the treatment of glioblastoma multiforme (GBM) in combination with temozolomide in adults
who have been newly diagnosed. It is also approved for treatment of recurrent GBM after
surgical and radiation options have been exhausted. Treatment involves wearing a device
resembling a bathing cap that delivers electromagnetic energy to the scalp.
Clinical trials
Clinical trials are research studies in which new treatments—drugs, diagnostics, procedures,
and other therapies—are tested in people to see if they are safe and effective. Research is
always being conducted to improve the standard of medical care. Information about current
clinical trials, including eligibility, protocol, and locations, are found on the Web. Studies can be
sponsored by the National Institutes of Health (see clinicaltrials.gov) as well as private industry
and pharmaceutical companies (see www.centerwatch.com).
Recovery & prevention
Self care
The primary care doctor and oncologist should discuss any home care needs with the
patient and the family. Supportive measures vary according to the symptoms. For example,
canes or walkers can help those having trouble walking. A plan of care to address changes in
mental status should be adapted to each patient’s needs.
Driving privileges may be suspended while taking anti-seizure medication. As each state
has different rules about driving and seizures, discuss this issue with the doctor.
Rehabilitation
Because brain tumors develop in parts of the brain that control movement, speech,
vision and thinking, rehabilitation may be a necessary part of recovery. Although the brain can
sometimes heal itself after the trauma of treatment, it will take time and patience. A
neuropsychologist can help patients evaluate changes caused by their brain tumor and develop
a plan for rehabilitation. A neuropsychological evaluation assesses the patient's emotional
state, daily behavior, cognitive (mental) abilities, and personality.
Physical therapy, occupational therapy, and speech therapy may be helpful to improve
or correct lost functions.
Recurrence
How well a tumor will respond to treatment, remain in remission, or recur after
treatment depends on the specific tumor type and location. A recurrent tumor may be a tumor
that still persists after treatment, one that grows back some time after treatment destroyed it,
or a new tumor that grows in the same place as the original one.
 When a brain tumor is in remission, the tumor cells have stopped growing or
multiplying. Periods of remission vary. In general, benign tumors recur less often than
malignant ones.
Since it is impossible to predict whether or when a particular tumor may recur, lifelong
monitoring with MRI or CT scans is essential for people treated for a brain tumor, even a benign
lesion. Follow-up scans may be performed every 3 to 6 months or annually, depending on the
type of tumor you had.
Links

 American Brain Tumor Association (www.abta.org) 1.800.886.2282

 National Brain Tumor Society (www.braintumor.org) 1.800.934.2873